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-Structure paper
タイトル | Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 2942, Year 2024 |
掲載日 | 2024年4月5日 |
著者 | Nazia Hussain / Ashish Apotikar / Shabareesh Pidathala / Sourajit Mukherjee / Ananth Prasad Burada / Sujit Kumar Sikdar / Kutti R Vinothkumar / Aravind Penmatsa / |
PubMed 要旨 | Pannexins are single-membrane large-pore channels that release ions and ATP upon activation. Three isoforms of pannexins 1, 2, and 3, perform diverse cellular roles and differ in their pore lining ...Pannexins are single-membrane large-pore channels that release ions and ATP upon activation. Three isoforms of pannexins 1, 2, and 3, perform diverse cellular roles and differ in their pore lining residues. In this study, we report the cryo-EM structure of pannexin 3 at 3.9 Å and analyze its structural differences with pannexin isoforms 1 and 2. The pannexin 3 vestibule has two distinct chambers and a wider pore radius in comparison to pannexins 1 and 2. We further report two cryo-EM structures of pannexin 1, with pore substitutions W74R/R75D that mimic the pore lining residues of pannexin 2 and a germline mutant of pannexin 1, R217H at resolutions of 3.2 Å and 3.9 Å, respectively. Substitution of cationic residues in the vestibule of pannexin 1 results in reduced ATP interaction propensities to the channel. The germline mutant R217H in transmembrane helix 3 (TM3), leads to a partially constricted pore, reduced ATP interaction and weakened voltage sensitivity. The study compares the three pannexin isoform structures, the effects of substitutions of pore and vestibule-lining residues and allosteric effects of a pathological substitution on channel structure and function thereby enhancing our understanding of this vital group of ATP-release channels. |
リンク | Nat Commun / PubMed:38580658 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.91 Å |
構造データ | EMDB-34265, PDB-8gtr: EMDB-34266, PDB-8gts: EMDB-34267, PDB-8gtt: EMDB-34268: human Pannexin1 |
化合物 | ChemComp-NAG: ChemComp-PTY: |
由来 |
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キーワード | MEMBRANE PROTEIN / Pannexins / large pore ion-channels / Pannexin1 / ATP release / large-pore ion channel / large-pore ion channel. |